Gemfibrozil Ciclosporin

Rhabdomyolysis has been reported in 3 lung transplant patients and 2 heart transplant patients when itraconazole was used in combination with ciclosporin. However, in three of these cases the concurrent use of simvastatin and in one case concurrent simvastatin and gemfibrozil would also have been factors, " as both ciclosporin and itraconazole can increase simvastatin levels (see Statins -i- Ciclosporin , p.l097, and also Statins + Azoles , p.l093). 

The use of bezafibrate with ciclosporin has resulted in significantly increased serum creatinine and reductions, no change, or increased serum ciclosporin levels. The use of fenofibrate has also been associated with reduced renal function and possibly reduced serum ciclosporin levels. Two studies found no pharmacokinetic interaction between ciclosporin and gemfibrozil while a third found gemfibrozil caused a significant reduction in ciclosporin levels. 

Two other transplant patients (one kidney and the other heart) had a reversible deterioration in renal function when they were given bezafibrate. This was severe in one, and the other had the effect on two occasions. Neither had any changes in ciclosporin blood levels. Two other similar cases have been reported, one of whom was subsequently given gemfibrozil without problems. ... 

Forty kidney transplant patients taking ciclosporin had a reduction in their hypertriglyceridaemia when gemfibrozil was added, and their ciclosporin blood levels and serum creatinine remained unaltered. Another study in 12 patients similarly found that gemfibrozil did not affect ciclosporin blood levels. ... 

However, in contrast to these findings, another study in 7 kidney transplant patients with hyperlipidaemia found that gemfibrozil 450 mg once or twice daily was associated with a decline in trough ciclosporin levels. Levels declined from 93 to 76 nanograms/mL after 6 weeks of treatment and after dose increases in 3 patients the level at 3 months was... 

In order to reduce the risk of myopathy the CSM in the UK have advised that statins should be used with care in patients who are at increased risk of this adverse effect. Among other risk factors, they mention concomitant use with fibrates, such as gemfibrozil , (p.llOO), and with inhibitors of CYP3A4 such as ciclosporin , (p.l097), macrolides ,(p.ll04), azoles , (p.l093), and protease inhibitors , (p.1108). They also recommend that patients should be made aware of the risks of myopathy and rhabdomyolysis, and asked to promptly report muscle pain, tenderness, or weakness, especially if accompanied by malaise, fever, or dark urine. A 2002 advisory on the use of statins gives some important safety recommendations, which are useful in the context of interactions ... 

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